Drug Company Halts Trials of Procrit November 27, 2003 By ANDREW POLLACK Several clinical trials of a widely used anemia drug have been halted in the last few weeks after patients developed a higher-than-expected number of blood clots, according to doctors and Johnson & Johnson, the seller of the drug. The development has added more evidence that the drug, Procrit, and perhaps similar drugs sold by Amgen, could pose risks if used more than is necessary to reverse anemia, doctors said. But several doctors said the drugs would not pose a danger if used in appropriate amounts. Procrit is a version of erythropoietin, or EPO, a natural hormone that stimulates the body to produce oxygen-carrying red blood cells. Procrit and two versions of EPO sold by Amgen, Epogen and Aranesp, have billions of dollars in combined sales annually, making EPO one of the best-selling drugs in the world. EPO is used primarily to treat anemia caused by cancer chemotherapy or kidney failure. The halt in the clinical trials was discussed on Monday in a report by Meirav Chovav, the biotechnology analyst at UBS, though some of the information had previously been reported by The Cancer Letter, a newsletter. In her report, titled "Is there a dark side to EPO?" Ms. Chovav said the new findings could slow the sales growth of Amgen's Aranesp. Robert DeLap, vice president for global regulatory affairs at Johnson & Johnson's pharmaceutical development unit, said the company suspended four clinical trials because of unexpected levels of blood clotting. Some other trials involving Procrit have also been halted or changed by their investigators as a precaution, according to doctors involved in those trials. Dr. DeLap said he could not quantify the extent of the extra blood clotting nor say whether there were any deaths. He said he did not expect the Food and Drug Administration to require any action because the trials have stopped. The trials were aimed at raising levels of hemoglobin, the oxygen-carrying molecule in the blood, to levels beyond that needed merely to treat anemia, Dr. DeLap said. The idea was that higher oxygen levels in the blood would make the radiation or chemotherapy being used to treat the patients' cancer more effective. "The goal is to push the hemoglobin up to higher levels than we would ordinarily expect from the therapeutic use of erythropoietin to reverse anemia," Dr. DeLap said. "When used as indicated for reversal of anemia, we don't have the same kind of concerns." Michael Beckerich, a spokesman for Amgen, also dismissed any concerns about risks or effect on Amgen's sales, saying the labels of the EPO drugs already contain warnings about the risk of blood clots. "This is not something new, that if you raise hemoglobin too fast, too hard, you might have problems," he said. Some doctors agreed. "There's nothing about any of these reports that would make use of erythropoietin in its current F.D.A. indications be considered dangerous," said Walter Curran, chairman for radiation oncology at Jefferson Medical College in Philadelphia, who was involved in one trial that was stopped. Still, Amgen and Johnson & Johnson had been hoping they could expand the market for their drugs by showing that they help treat cancer, not just anemia. There was some justification for that, since doctors have long known that radiation therapy works better in the presence of oxygen. "Based on the data that was available we thought this was something that was going to not only help our patients feel better but also live longer," said Frankie Ann Holmes, co-director for breast medical oncology research at U.S. Oncology, a company that manages cancer practices. Now, she says, "there is mounting evidence that it is not helpful and indeed it is harmful." The blood clots are the second blow to the idea of using EPO to help treat cancer. A study published last month in The Lancet, the London-based medical publication, showed that an EPO drug made by Roche did not prolong life and might have even impaired treatment. That study, and one in Canada that reached a similar conclusion, have been criticized by others for poor design and execution, leaving the matter far from settled. Still, Dr. DeLap said Johnson & Johnson had decided for now not to sponsor any more trials to see whether EPO could improve the effectiveness of radiation or chemotherapy. In her report, Ms. Chovav of UBS said the clotting problems were being seen now because the drugs are being used to treat milder cases of anemia, whereas originally they were used mainly for more serious cases. The companies are advertising to patients with milder anemia, she said, because they represent the biggest untapped market. But the new data could slow such sales, she said. "We anticipate that physicians will be less receptive to patient requests for therapy in light of this data," she wrote, "and that once patients are informed of the potential risk of EPO, they may decide to forgo this therapy." Other analysts did not agree. The stocks of the two companies did not fall Monday. Yesterday, shares of Johnson & Johnson fell 99 cents, to $49.70, and those of Amgen fell 77 cents, to $58.14. Increased use of Amgen's Epogen, for kidney dialysis patients, also seems to be occurring. A survey of Medicare claims of 79,000 dialysis patients found that the starting dose of EPO has risen sharply since 1996, even for patients with only mild anemia. In 2001, 58 percent of the patients received an initial dose of EPO higher than recommended in National Kidney Foundation guidelines, up from 34 percent in 1996, according to the study by U.S. Renal Data System in Minneapolis. In a recent report, SG Cowen biotechnology analysts said dialysis centers tended to overuse EPO because their Medicare reimbursement were greater than what they pay for the drug. About 30 percent of dialysis patients, the analysts said, have hemoglobin levels above the kidney foundation guidelines. Brian Pereira, president of the National Kidney Foundation, said EPO was not being overused and that dialysis patients do not face risk of blood clots. "Dialysis patients are different from chemotherapy and cancer patients," he said. Cancer patients have "an inherent tendency to clot" while dialysis patients tend more to bleed. Dr. Pereira, who is also president of the New England Health Care Foundation at Tufts-New England Medical Center, said EPO doses had increased because "more and more patients are getting into the target range" for hemoglobin. He said that even the target range was lower than the levels of hemoglobin in many healthy people. http://www.nytimes.com/2003/11/27/business/27drug.html?ex=1070941817&ei=1 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.